Immunology: An Overview

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Immunology An Overview

• Part 2

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Outline Part 2

• Review of Part 1
• B cells and humoral immunity
• T cells and cellular immunity
• Tolerance and autoimmunity

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Review of Part 1

• Immunity refers to all of the mechanisms used by
  the body to protect itself from foreign
  challenges
• Described as early as 430 B.C., Immunology began
  to be studied widely at the beginning of the 20th
  century
• The primary function of the immune system is to
• Distinguish between self and non-self
• Eliminate non-self threats (e.g. bacteria,
  viruses)
• Remain tolerant to self

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Review of Part 1 (continued)

• The two main branches of the immune system are
  the innate and acquired immune responses

• The immune system consists of a collection of
  cells distributed throughout various organs and
  tissues of the body

• The immune system can fail in three main ways
• Hypersensitivity
• Immunodeficiency
• Autoimmunity

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Lymphocyte Subsets
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B Lymphocytes

• First identified as being produced in the bursa
  of fabricius in birds

• In humans, B cells are produced in the bone
  marrow (in adults) and fetal liver

• Primary effectors of humoral immunity (via
  antibody production)

• Two main groups of B cells antibody producing
  (plasma cells) and memory cells

• Recognize antigen by means of surface-expressed
  antigen receptors

• Generally dependent on T cell help

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Antigens and Antibodies - I

• Antigen - derived from antibody generating now
  understood to mean a compound which elicits
  either a cellular or humoral immune response

Hapten/Carrier Response

• Can be protein or large polysaccharide

• Smaller molecules (e.g. lipids, DNA) can be
  antigenic when coupled to carrier proteins.
  These antigens (called haptens) can then bind
  antibody free from carrier.

• Specific regions of antigen (known as epitopes or
  antigenic determinants) interact with/are
  recognized by antibodies

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Antigens and Antibodies - II

• CHARACTERISTICS OF AN ANTIGEN
• Must not be too small or it will be excreted
  before it elicits an immune response
• Must either be foreign (non-self) or normally
  hidden from immune system
• Must have a stable secondary and tertiary
  structure. For example, lipids are so fluid that
  they do not have a consistent shape to be
  recognized by the antibody. (A key made out of
  butter will not open a lock.)

Essentials of Immunology, 1998, GSM, Inc.
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Antigens and Antibodies - III

• Antibodies are soluble, multi-subunit members of
  a glycoprotein family known as immunoglobulins
  (Igs)

• Recognize and bind to specific antigens

Y

• Binding of antigen occurs at the two
  variable-region sites. On a given antibody
  molecule, these two sites have the same
  specificity. This allows crosslinking of
  antigen by antibody

Y
Y
Y
Y
Y
Y
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Antigens and Antibodies - III
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Clonal Selection
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Antibody-Producing Plasma Cells
Y
Memory Cells
Y
Y
Y
Y
Y
Y
Y
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Immunogenetics

• A single gene contains infor-mation for
  production of a single protein

• The human genome has between 80,000 and 100,000
  genes

• It has been estimated that humans can respond to
  100 million different antigens

HOW ?!?!
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Immunological Memory
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Lymphocyte Subsets
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T Lymphocytes

• T cells derive from stem cells in the bone
  marrow, mature in the thymus, and then are
  released into the periphery

• Similarities between T and B cells
• Antigen receptor on surface (T cell receptor)
• Recognize single, specific antigen
• Expand through clonal selection
• Some T cells exist as long-lived memory cells

• T cell production decreases during adolescence,
  due to thymic involution

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Antigen Processing and Presentation
Unlike B cells, T cells cannot recognize free
antigen it must be

• Processed (digested) in to smaller fragments
  within special antigen presenting cells (APCs)

• Presented on the surface of APCs in the context
  of MHC (major histocompatibility complex) proteins

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T Cell Development and Thymic Maturation
Approximately 95 of all thymocytes die in the
thymus!!!
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Cytotoxic (Killer) T Cells
Cytotoxic T cells (CD8 T cells) attack their
target cells (e.g. virally-infected cells) and
kill them directly..
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Helper T Cells
Helper T cells (CD4 T cells) produce proteins
(cytokines) which act on B cells, stimulating
them to produce antibodies
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Clonal Deletion
X
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What Causes Autoimmunity?
Death of Autoreactive T or B Cell (Clonal
Deletion)
Normal Immune Response
Autoimmune Response
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Why Do We Care About All Of This?

• Diseases Associated With Immune System
  Malfunction
• AIDS
• Leukemia and other cancers
• Arthritis
• Multiple Sclerosis
• Diabetes
• Allergies
• Infectious diseases
• Transplant rejection

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Jory P. Weintraub, Ph.D. jory_at_unc.edu (919)
843-9035 www.unc.edu/depts/cell/Jory/immunology/j
ordan1.ppt www.unc.edu/depts/cell/Jory/immunology/
jordan2.ppt